Inhibition of the Amygdala: Key to Pathological States?

Annals of the New York Academy of Sciences - Tập 985 Số 1 - Trang 263-272 - 2003
Gregory J. Quirk1, Donald R. Gehlert2
1Department of Physiology, Ponce School of Medicine, Ponce, Puerto Rico, 00732‐7004
2Lilly Research Laboratories, Indianapolis, Indiana 46285, USA

Tóm tắt

Abstract:The amygdala plays an important role in associating sensory stimuli with aversive or appetitive outcomes. Conditioning procedures potentiate inputs to the amygdala, which facilitate emotional responses via subcortical and cortical outputs. Powerful inhibitory circuits exist that control expression of conditioned responses in the amygdala, including inhibition from prefrontal cortex. Deficient inhibitory tone in the amygdala could lead to overexpression of conditioned responses, producing pathological states such as anxiety disorders and drug‐seeking behavior. Support for this comes from several lines of animal research: (1) GABA antagonist‐induced priming of anxiety states, (2) extinction of conditioned fear, (3) modulation of inhibitory avoidance memory, and (4) cue‐induced reinstatement of drug seeking. Cue‐induced craving in humans is associated with feelings of fear and autonomic arousal, suggesting a link between fear and addiction in the amygdala. Future therapies aimed at increasing inhibitory tone in the amygdala, either locally or via the prefrontal cortex, may prevent anxiety disorders and addiction relapse. Novel neuropeptides, which can either excite or inhibit specific components of anxiety responses, offer promise in this regard.

Từ khóa


Tài liệu tham khảo

Davis M. 2000. The role of the amygdala in conditioned and unconditioned fear and anxiety.InThe Amygdala. J.P. Aggleton Ed. :213–288. Oxford. New York.

Dolan R.J. 2000. Functional neuroimaging of the amygdala during emotional processing and learning.InThe Amygdala. J.P. Aggleton Ed. :631–654. Oxford. New York.

10.1016/S0149-7634(99)00016-0

10.1146/annurev.neuro.23.1.155

McGaugh J.L. B. Ferry A. Vazdarjanova & B. Roozendaal. 2000. Amygdala: role in modulation of memory storage.InThe Amygdala. J.P. Aggleton Ed. :391–424. Oxford. New York.

Everitt B.J. R.N. Cardinal J. Hall et al.2000. Differential involvement of amygdala subsystems in appetitive conditioning and drug addiction.InThe Amygdala. J.P. Aggleton Ed. :353–390. Oxford. New York.

Gallagher M. 2000. The amygdala and associative learning.InThe Amygdala. J.P. Aggleton Ed. :311–330. Oxford. New York.

10.1037/0033-295X.108.3.483

10.1037/0033-295X.108.1.4

Rosenkranz J.A., 2002, Cellular mechanisms of infralimbic and prelimbic prefrontal cortical inhibition and dopaminergic modulation of basolateral amygdala neurons in vivo, J. Neurosci., 22, 324, 10.1523/JNEUROSCI.22-01-00324.2002

LeDoux J.E. 1996. The Emotional Brain. Simon & Schuster. New York.

Hyman S.E., 1998, Brain neurocircuitry of anxiety and fear: implications for clinical research and practice, Biol. Psychiatry, 44, 1201

10.1046/j.1460-9568.2000.00281.x

Paré D., 2000, Neuronal correlates of fear in the lateral amygdala: multiple extracellular recordings in conscious cats, J. Neurosci., 20, 2701, 10.1523/JNEUROSCI.20-07-02701.2000

10.1016/0896-6273(95)90092-6

10.1038/89512

10.1038/37601

10.1038/37605

10.1038/71145

10.1038/41097

10.1162/jocn.1989.1.3.238

10.1523/JNEUROSCI.19-23-10575.1999

10.1016/0166-4328(85)90087-7

10.1016/0091-3057(95)00153-N

10.1016/0006-8993(95)00915-D

Sajdyk T.J., 1997, Excitatory amino acid receptor antagonists block the cardiovascular and anxiety responses elicited by gamma‐aminobutyric acidA receptor blockade in the basolateral amygdala of rats, J. Pharmacol. Exp. Ther., 283, 969

10.1016/S0006-8993(97)00594-5

10.1016/S0014-2999(00)00128-X

Pavlov I. P. 1927. Conditioned Reflexes. Oxford University Press. London.

Gorman J.M., Am. J. Psychiatry, 157, 493, 10.1176/appi.ajp.157.4.493

10.1111/j.1749-6632.1997.tb48264.x

10.1016/0304-3940(93)90241-C

10.1016/S0306-4522(99)00014-7

Quirk G.J., 2000, The role of medial prefrontal cortex in recovery of extinguished fear, J. Neurosci., 201, 6225, 10.1523/JNEUROSCI.20-16-06225.2000

10.1016/0306-4522(95)00417-3

10.1002/1096-9861(20000710)422:4<556::AID-CNE6>3.0.CO;2-U

10.1016/S0006-3223(98)00297-2

10.1016/S0006-3223(01)01215-X

10.1126/science.287.5451.248

10.1073/pnas.91.18.8477

10.1016/S0959-4388(02)00306-9

10.1038/371702a0

10.1073/pnas.93.15.8016

10.1016/S0006-3223(99)00219-X

10.1016/S1364-6613(98)01271-6

10.1046/j.1460-9568.2002.01889.x

10.1016/0306-4522(95)00125-3

10.1016/S0166-4328(96)02270-X

10.1016/S0893-133X(99)00157-8

10.1016/S0893-133X(01)00371-2

10.1176/ajp.156.1.11

10.1016/S0006-3223(01)01269-0

10.1007/s002130000499

Stewart J., 2000, Pathways to relapse: the neurobiology of drug‐ and stress‐induced relapse to drug‐taking, J. Psychiatry Neurosci., 25, 125

10.1007/s002130000642

10.1007/s002130000636

10.1037/0735-7044.113.5.891

10.1093/oxfordjournals.aje.a115166

File S.E. 2000. The amygdala: anxiety and benzodiazepines.InThe Amygdala. J.P. Aggleton Ed. :195–212. Oxford. New York.

Niehoff D.L., 1983, Benzodiazepine receptors: localization in rat amygdala, J. Neurosci., 3, 2091, 10.1523/JNEUROSCI.03-10-02091.1983

10.1016/S0166-4328(98)00132-6

10.1016/S0006-8993(00)02638-X

10.1016/S0091-3057(01)00679-7

10.1016/S0014-2999(99)00018-7

10.1038/nature01138

Thông tin
Thông tin xuất bản

Annals of the New York Academy of Sciences

Tập 985 Số 1

263-272

Thông tin tác giả